At physiological pH means at the pH in your body, it's varies depending on the body part and diet and things, but in the sinuses I think it's around pH 6. Ionised means the water soluble form, and non-ionised means the freebase form. This article interests me for several reasons, firstly because I never knew the pKa of heroin, and and as it's only 7.6, it surprises me how mild this is. Now mescaline and methamphetamine IIRC both have pKa's above 12, which means if you snort the freebase form of those you'll get chemical burns. So this means that snorting heroin freebase shouldn't really burn at all.
Now in order to pass the blood-brain barrier the non-polar compounds get transported, but ionised compounds don't make it across. In order to be water soluble the heroin has to be in it's ionised form. But then your body strips off the acid part and transports the freebase part into your brain. When the article states: "At physiologic pH on average 40% of heroin will be in a nonionised form and therefore accessible for membrane-transport", it means that when you snort heroin freebase, you'll be able to directly absorb 40% of it.
This is surprising to me, because it's water soluble substances that get absorbed rapidly. But it makes sense because smoked freebases are extremely rapidly absorbed by the lungs. And if they can absorb freebases, the sinus should be able to. But theres a difference, in that smoked stuff consists of microscopic sized particles spread over a very wide surface area in the lungs. But snorted stuff is very clumpy and spread over a relatively tiny surface area.
Also if 40% of the heroin is non-ionised, that doesn't necessarily mean that the other 60% is water soluble and instantly absorbed. What happens is when you snort it 40% is capable of being transported across the membranes, the other 60% will have to find a hydrogen ion in the area, become ionised which makes it water soluble and be absorbed the same way your nose absorbs water. There's not a large amount of free hydrogen ions in your nose, because if there were, then your nose would be extremely acidic, and not around a mild pH 6. So all of the free hydrogen ions would bind onto the heroin, then it would take a while for more free hydrogen ions to get transported to that area.
If you snort heroin hydrochloride, 100% of it is ionised, so it doesn't have to wait for a free hydrogen ion to bind to before it becomes water soluble and absorb along with any water. So it's complicated and you can't really say that because heroin hydrochloride is 0% non-ionised, therefore 0% gets membrane transported into the body. Because it does get absorbed, and rapidly at that, but heroin hydrochloride just needs to gets absorbed before the hydrochloride molecule gets stripped off, and the heroin freebase get transported across membranes into your brain. But heroin freebase can be absorbed directly.
But again, transport across the membranes work a bit like a ferry, it proceeds at a set rate and has a limited capacity. So if you inject heroin, it's shot into the blood and there's a huge number of sites for the hydrochloride to get stripped off. But if you snort it, it still will get absorbed, but because the local transport sites are swamped, there's a queue and it takes time for everything to get absorbed. Which is why smoking or rectal administration is far more efficient then snorting, because there's a much greater surface area and blood supply.
Anyways, I learned here that even heroin freebase is snortable